In experimental animal studies, caloric restriction has been shown to improve myocardial ischemic tolerance and increase serum adiponectin levels. In this paper, Shinmura et al. investigated the specific role of adiponectin in caloric restriction-induced cardioprotection and analyzed the oligomeric state of circulating adiponectin in adiponectin antisense transgenic mice. They demonstrated that circulating adiponectin levels must increase in order to achieve the cardioprotective effects observed following short-term caloric restriction. They also found that production of the high-molecular-weight form of adiponectin increased during caloric restriction. This form is associated with activation of AMP-activated protein kinase (AMPK). The authors also identified that this key enzyme plays a significant role in the cardioprotection afforded by short-term caloric restriction. These observations led the authors to conclude that the cardioprotective effects of short-term caloric restriction are mediated by increased production of adiponectin and associated AMPK activation. This paper was accompanied by an editorial by Jason R.B. Dyck who recognized that the Shinmura study provides valuable insights into the effects of short-term caloric restriction on the heart. However, the author highlights a number of unanswered questions. For example, he underlines the importance of clarifying whether the cardioprotective effects of adiponectin can be attributed directly to AMPK activation or to other pathways, and whether short-term caloric restriction and activation of AMPK are beneficial in models of ischemia/reperfusion injury that include clinically relevant concentrations of fatty acids. Dyck also suggests that the adiponectin-AMPK signalling axis may be an effective therapeutic strategy in patients with progressive ischemic heart disease at high risk of developing acute myocardial infraction, even in the absence of obesity.
Documentation centre